Histidine decarboxylase from Lactobacillus 30a is the best known example of a growing number of pyruvoyl enzymes that catalyze production of certain amines in bacterial, yeast, and mammalian tissues. This enzyme is stable and readily available; both the active enzyme containing two dissimilar subunits, (Alpha Beta)6, and an inactive mutant proenzyme containing a single type subunit, Pi6, are readily prepared in homogeneous, crystalline form. They thus provide excellent models for studying the biogenesis of pyruvoyl enzymes, their mechanism of action, and their three-dimensional structure. As a step toward these objectives, this project is aimed at: (1) completing the amino acid sequence of the homogeneous enzyme and proenzyme by use of (a) standard procedures for sequencing proteins and (b) in collaboration with an independent group, by cloning the decarboxylase gene and determining the nucleotide sequence of the isolated gene; (2) using this sequence information to aid in elucidation of the 3-dimensional structure of these proteins in an independent, ongoing, collaborative x-ray crystallographic study; (3) determining and comparing the chemical nature of activation of both wild-type and mutant proenzyme, a process that involves an apparently non-proteolytic cleavage of a precursor peptide chain (Pi) into the dissimilar Alpha, Beta subunits of the active enzyme; (4) covalent modification studies of the native enzyme, and isolation of additional mutant enzymes to determine how changes modify native structure and catalytic activity of the enzyme. Such information, when available, should permit the reaction mechanism of this and perhaps related enzymes to be specified in detail, as well as the mechanism of its biogenesis from its proenzyme. The physiological role of this enzyme in bacteria is not yet established. Its major product, histamine, has many effects (e.g., on secretion of gastric HCl, blood pressure, allergic and inflammatory reactions) in higher animals. Since bacteria that produce this enzyme are intestinal inhabitants, a role for the enzyme in the commensal interactions of host and bacteria appears likely.